The liver is the major site of covalent binding of ultimate carcinogens after oral doses of most precarcinogens and usually the microsomal mixed function oxidases show greatest activity in this organ. Tumors may not appear, however, in the livers of adult animals exposed to high single doses of carcinogens that can induce cancer in other organs where the covalent binding may be much less. The induction of cancer appears to depend on the nature of the ultimate carcinogen, the extent of its binding to the target macromolecule and the capacity of cellular repair processes, as well as various systemic factors. These conclusions are based largely on experiments with simple methylating and ethylating nitroso compounds and have led to a hypothesis that the liver may play a part in preventing or reducing the incidence of cancer in other organs, following oral ingestion of chemical precarcinogens. This hypothesis will be tested, particularly at low dose levels with other carcinogens including other nitroso compounds, 7,12-dimethylbenz(a)anthracene, 2-acetylaminofluorene, aflatoxin B1 carbon tetrachloride, vinyl chloride and other chlorinated hydrocarbons. The methods used will include measurements of the extent and persistence of binding to DNA and other macromolecules in different organs, DNA repair, using newly developed fluorimetric procedures and pathological studies of cancer incidence and development in carcinogen treated rodents. BIBLIOGRAPHIC REFERENCES: Sarma, D.S.R., Rajalakshmi, S. and Farber, E. Chemical carcinogenesis: interactions of carcinogens with nucleic acids, in: Cancer, a comprehensive treatise, vol. 1 Etiology: Chemical and physical carcinogenesis, F.F. Becker (ed), pp 235-287, Plenum Press, New York, 1975. Farber, E. International Symposium on Gene Expression and Carcinogenesis in Cultured Liver: Summary and some conclusions, in: Gene Expression and Carcinogenesis in Cultured Liver, L.E. Gerschenson and E. Brad Thompson (eds), pp.488-491, Academic Press, New York, 1975.